• Journal of Life Science
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• v.34 no.6
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• pp.399-407
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• 2024

Angiogenesis is the process by which new blood vessels form from existing blood vessels. This phenomenon occurs during growth, healing, and menstrual cycle changes. Angiogenesis is a complex and multifaceted process that is important for the continued growth of primary tumors, metastasis promotion, the support of metastatic tumors, and cancer progression. Impaired angiogenesis can lead to cancer, autoimmune diseases, rheumatoid arthritis, cardiovascular disease, and delayed wound healing. Currently, there are only a handful of effective antiangiogenic drugs. Recent studies have shown that natural marine products exhibit antiangiogenic effects. In a previous study, we reported that the hexane extract of H. fusiformis (HFH) could inhibit the development of new blood vessels both in vitro and in vivo. The aim of this study was to describe the inhibitory effect of chloroform extracts of H. fusiformis on angiogenesis. To investigate how chloroform extract prevents blood vessel growth, we examined its effects on HUVEC, including cell migration, invasion, and tube formation. In a mouse Matrigel plug assay, H. fusiformis chloroform extract (HFC) also inhibited angiogenesis in vivo. Certain proteins associated with blood vessel growth were reduced after HFC treatment. These proteins include vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK)/extracellular signal transduction kinase, and serine/threonine kinase 1 (AKT). These studies have shown that the chloroform extract of H. fusiformis can inhibit blood vessel growth both in vitro and in vivo.

• Animal cells and systems
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• v.15 no.4
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• pp.268-273
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• 2011

Transgenic mice expressing green fluorescent protein (GFP) under the control of human glial fibrillary acidic protein promoter (hGFAP) have been utilized for in vivo labeling of astrocytes. Although it has been considered that virtually all astrocytes express GFP in this transgenic mouse, we found that different subsets of GFAP-expressing astrocytes express considerably different levels of GFP in the adult brain. Astrocytes in the spinal cord, the molecular layer of thecerebellum, meninges, white matter, corpus callosum and blood vessels exhibited strong GFP, whereas subsets of astrocytes associated with granule cells in the cerebellum and dentate gyrus did not or only marginally exhibited GFP. We also found that a small subset of GFP-expressing cells in the periglomeruli of the olfactory bulb did not express GFAP immunoreactivity. Collectively, these results suggest that human GFAP promoter-derived GFP expression does not faithfully recapitulate the endogenous GFAP expression in mice, suggesting that upstream regulatory mechanisms controlling GFAP transcription are different in different populations of astrocytes, and may reflect the functional diversity of astrocytes.

• Biomolecules & Therapeutics
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• v.2 no.3
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• pp.247-255
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• 1994

As a series of safety studies of DA-3030, a new rhO-CSF, its local irritancy was examined in the rabbits after the following treatment; application into the conjunctival sac of the eye(single), subcutaneous injection(single), intramuscular injection(single), and intravenous injection(8-day repeated). In addition, paravenous irritation of DA-3030 was investigated in mice. The results obtained were as follows. 1. In the result of ocular irritation test, 0.03% solution of DA-3030 could be considered as a non-irritating material. 2. The local irritation of DA-3030 by an injection of 0.5mι of its solution subcutaneously or intramuscularly was negligible and not so much different from that of saline. 3. In the vascular irritancy test, macro- and microscopic observations revealed that the irritating activity of DA-3030 in blood vessels was not different from that of saline when they were injected once a day into vein retroauricularis of rabbits for 8 days.4. The paravenous administration of DA-3030 did not induce any abnormal changes at injection sites except mild swelling in 1 mouse at 3 hours after injection which was thought to be due to slow absorption. The above-mentioned results suggest that DA-3030 has no irritating activity when injected through intravenous or subcutaneous route for clinical practice as 0.03% solution.

• Journal of Periodontal and Implant Science
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• v.23 no.3
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• pp.605-621
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• 1993

The gingival hyperplasia refers to an increase in the size of the gingival tissue produced by an increase in the number of its component cells. In order to investigate the cellular change in epithelium and subepithelial tissue of noninflammatory gingival hyperplasia, the gingival tissues were surgically obtained from the patients with dilantin gingival hyperplasia and idiopathic gingival hyperplasia. The excised tissue samples were fixed in neutral formalin for 6-24 hours, embedded with paraffin, sectioned at $4-6{\mu}m$ in thickness, mounted on glass slides coated with 3-aminopropyltriethoxysilane(Sigma Chemical Co., St. Louis, MO, U.S.A.) and immunocytochemically processed by Avidin-Biotin peroxidase complex method for detecting proliferating cell nuclear antigen, tenascin and collagen type IV. Monoclonal mouse anti-human PCNA antibody(Oncogene Science, Uniondale, NY, U.S.A., 1 : 250,000), monoclonal mouse anti-human tenascin antibody(Chemicon-International Inc., Temecula, CA, U.S.A., 1:5,000), and monoclonal mouse anti-human collagen type IV(Dakopatts, Glostrup, Denmark, 1: 50) were used as primary antibodies. The results were as follows: 1. In non-inflammatory gingival hyperplasia, the positive reaction to proliferating cell nuclear antigen was localized in the basal cell layer of gingival epithelium and well-developed rete pegs. 2. The positive reaction to tenascin was shown in the connective tissue subjacent to basament membrane of gingival tissue, and especially strong positive reaction was noted in the tip portion of connective tissue projections. 3. The positive reaction to collagen type IV was localized along the basement membranes of gingival epithelium and blood vessels. The results suggest that connective tissue enlargement may affect the proliferation of gingival epithelium.

• Journal of Ginseng Research
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• v.46 no.2
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• pp.275-282
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• 2022

Background: Stroke is a neurological disorder characterized by brain tissue damage following a decrease in oxygen supply to brain due to blocked blood vessels. Reportedly, 80% of all stroke cases are classified as cerebral infarction, and the incidence rate of this condition increases with age. Herein, we compared the efficacies of Korean White ginseng (WG) and Korean Red Ginseng (RG) extracts (WGex and RGex, respectively) in an ischemic stroke mouse model and confirmed the underlying mechanisms of action. Methods: Mice were orally administered WGex or RGex 1 h before middle cerebral artery occlusion (MCAO), for 2 h; the size of the infarct area was measured 24 h after MCAO induction. Then, the neurological deficit score was evaluated and the efficacies of the two extracts were compared. Finally, their mechanisms of action were confirmed with tissue staining and protein quantification. Results: In the MCAO-induced ischemic stroke mouse model, WGex and RGex showed neuroprotective effects in the cortical region, with RGex demonstrating superior efficacy than WGex. Ginsenoside Rg1, a representative indicator substance, was not involved in mediating the effects of WGex and RGex. Conclusion: WGex and RGex could alleviate the brain injury caused by ischemia/reperfusion, with RGex showing a more potent effect. At 1,000 mg/kg body weight, only RGex reduced cerebral infarction and edema, and both anti-inflammatory and anti-apoptotic pathways were involved in mediating these effects.

• Proceedings of the KSME Conference
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• 2008.11a
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• pp.1404-1408
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• 2008

The migration and proliferation of vascular endothelial cells (VEC), which play an important role in vascular remodeling, are known to be regulated by hemodynamic forces in the blood vessels. When shear stresses of 2, 6, 15 dynes/$cm^2$ are applied on mouse micro-VEC in vitro, cells surprisingly migrate against the flow direction at all conditions. While higher flow rate imposes more resistance against the cells, reducing their migration speed, the horizontal component of the velocity parallel to the flow increases with the flow rate, indicating the higher alignment of cells in the direction parallel to the flow at a higher shear stress. In addition, cells exhibit substrate stiffness and calcium dependent migration behavior, which can be explained by polarized remodeling in the mechanosensitive pathway under shear stress.

• Molecules and Cells
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• v.38 no.12
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• pp.1029-1036
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• 2015

Appropriate vessel development and its coordinated function is essential for proper embryogenesis and homeostasis in the adult. Defects in vessels cause birth defects and are an important etiology of diseases such as cardiovascular disease, tumor and diabetes retinopathy. The accumulative data indicate that ETV2, an ETS transcription factor, performs a potent and indispensable function in mediating vessel development. This review discusses the recent progress of the study of ETV2 with special focus on its regulatory mechanisms and cell fate determining role in developing mouse embryos as well as somatic cells.

• Clinical and Experimental Reproductive Medicine
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• v.27 no.1
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• pp.31-37
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• 2000

This study was designed to identify the ultrastructural changes of mouse endometrium during peri-implantation period and obtain the fundamental information for the establishment of 3-dimensional culture system of mouse endometrial cells in vitro. The used female ICR mice ($6{\sim}8$ wks) were conducted on pregnant. The biopsies were obtained from whole uterus at cycle day 1 (D1) and day 5 (D5) after hCG injection and mating. The biopsies materials were fixed 2.5% glutaraldehyde and 1% osmium tetroxide. Subsequently, for observation using light and transmission electron microscopy (LM and TEM), they were dehydrated and embedded in Epon and the embedded biopsies were sectioned and stained. For scanning electron microscopy (SEM), the fixed specimens were dehydrated, dried and coated with gold. 1) For LM, the biopsied materials at D5 (late secretory phase) were appeared the extended stromal layer by increased connective tissues and the fully developed endometrial glands and vessels compared with D1 (early secretory phase). 2) For TEM, the mouse endometrium was consisted of 3-layers, a simple polarized columnar epithelial cells, basement membrane and stromal cells. At D5, the distribution of microvilli, endoplasmic reticulum, Golgi body, lipid and glycogen deposits, secretory granules and surface area of basement membrane were increased. 3) For SEM, the degree of folding and microvilli of surface of mouse epithelial cells was became more and more according to the process of secretory phase, and at D5, implantation time of mouse, the appearance of pinopodes as a specific marker of uterine receptivity was found. The uterine pinopodes of mouse were found in narrow sites at the luminal surface, irregularity and appeared the different stages in the same sample. Therefore, these results indicated that the mouse endometrium was experienced dramatic morphological changes during peri-implantation period.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.5
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• pp.353-359
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• 2010

Introduction: This study examined the effect of cyclosporine A (CsA) on the allogenic cranial bone graft in the mice. Materials and Methods: Twenty eight 12-week-old male ICR mice weighing 40 g were used. The experimental group was injected subcutaneously with CsA (10 mg/kg/day) diluted in Caster oil for 7 days prior to the graft until sacrifice. The control group was injected with the same solution without CsA. Two full-thickness bone defects with a diameter of 3 mm were made with a trephine bur in the parietal bone lateral to the sagittal suture. A calvarial defect of a mouse was grafted with allogenic calvarial bone disc from another mouse. The experimental and control groups were injected with CsA and the solution without CsA in the same manner before surgery, respectively. The mice were sacrificed at 1 week, 2 weeks and 4 weeks after the bone graft, respectively. Results: In the experimental group, fibrous connective tissues and small amounts of inflammatory cells were observed. At 2 weeks after the allograft in the experimental group, new bone formation in fibrous collagenous tissue and around the allogenic bone was noted. At 4 weeks after the allograft, new bone formation was active along and at the periphery of the mature allogenic bone. The proliferation of blood vessels increased in bone marrow. In the control group, fibrous tissues and inflammatory cells were observed around the allogenic bone and existing bone at 1 week. At 2 weeks after the allograft, the proliferation of blood vessels accompanied by inflammatory cells were scattered in the fibrous connective tissues. New bone formation around the allogenic and existing bone could be observed. At 4 weeks after the allograft, inflammatory cells were severely infiltrated around the allogenic bone. Osteoclasts were scattered along the allogenic bone and induced bone resorption. Conclusion: These results suggest that the daily administration of CsA (10 mg/kg/day) induces efficient immunosuppression without serious complications, and this protocol might be useful for the experimental model of allogenic bone grafts.

• Journal of Life Science
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• v.33 no.9
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• pp.703-712
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• 2023

Angiogenesis, the formation of blood vessels from pre-existing vessels, is a multistep process regulated by modulators of angiogenesis. It is essential for various physiological processes, such as embryonic development, chronic inflammation, and wound repair. Dysregulation of angiogenesis causes many diseases, such as cancer, autoimmune diseases, rheumatoid arthritis, cardiovascular disease, and delayed wound healing. However, the number of effective anti-angiogenic drugs is limited. Recent research has focused on identifying potential drug candidates from natural sources. For example, marine natural products have been shown to have anti-cancer, anti-oxidant, anti-inflammatory, antiviral, and wound-healing effects. Thus, this study aimed to describe the angiogenesis inhibitory effect of Hizikia fusiforms (brown algae) extract. The hexane extract of H. fusiformis has shown inhibitory effects on in vitro angiogenesis assays, such as cell migration, invasion, and tube formation in human umbilical vein endothelial cells (HUVECs). The hexane extract of H. fusiformis (HFH) inhibited in vivo angiogenesis in a mouse Matrigel gel plug assay. In addition, the protein expression of vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK)/extracellular signal kinase, and AKT serine/threonine kinase 1 decreased following treatment with H. fusiformis extracts. Our results demonstrated that the hexane extract of H. fusiformis (HFH) inhibits angiogenesis in vitro and in vivo.